Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.

ABSTRACT: BACKGROUND:A growing number of studies clearly demonstrate a substantial association between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD), although little is known about the shared genetics that contribute to this association. METHODS:We conducted a large-scale cross-trait genome-wide association study to investigate genetic overlap between COPD (Ncase?=?12,550, Ncontrol?=?46,368) from the International COPD Genetics Consortium and four primary cardiac traits: resting heart rate (RHR) (N?=?458,969), high blood pressure (HBP) (Ncase?=?144,793, Ncontrol?=?313,761), coronary artery disease (CAD)(Ncase?=?60,801, Ncontrol?=?123,504), and stroke (Ncase?=?40,585, Ncontrol?=?406,111) from UK Biobank, CARDIoGRAMplusC4D Consortium, and International Stroke Genetics Consortium data. RESULTS:RHR and HBP had modest genetic correlation, and CAD had borderline evidence with COPD at a genome-wide level. We found evidence of local genetic correlation with particular regions of the genome. Cross-trait meta-analysis of COPD identified 21 loci jointly associated with RHR, 22 loci with HBP, and 3 loci with CAD. Functional analysis revealed that shared genes were enriched in smoking-related pathways and in cardiovascular, nervous, and immune system tissues. An examination of smoking-related genetic variants identified SNPs located in 15q25.1 region associated with cigarettes per day, with effects on RHR and CAD. A Mendelian randomization analysis showed a significant positive causal effect of COPD on RHR (causal estimate?=?0.1374, P?=?0.008). CONCLUSION:In a set of large-scale GWAS, we identify evidence of shared genetics between COPD and cardiac traits.

SUBMITTER: Zhu Z 

PROVIDER: S-EPMC6444755 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature